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Year : 2017  |  Volume : 9  |  Issue : 1  |  Page : 16-21  

Moisture sorption–desorption characteristics and the corresponding thermodynamic properties of carvedilol phosphate

Department of Chemistry, SRM University, Chennai, Tamil Nadu, India

Date of Web Publication15-May-2017

Correspondence Address:
Ravikiran Allada
Department of Chemistry, SRM University, Kattankulathur, Kancheepuram District, Chennai - 603 203, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0975-7406.206216

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Aims: Carvedilol phosphate(CDP) is a nonselective beta-blocker used for the treatment of heart failures and hypertension. In this work, moisture sorption–desorption characteristics and thermodynamic properties of CDP have been investigated. Materials and Methods: The isotherms were determined using dynamic vapor sorption analyzer at different humidity conditions(0%–90% relative humidity) and three pharmaceutically relevant temperatures(20°C, 30°C, and 40°C). The experimental sorption data determined were fitted to various models, namely, Brunauer–Emmett–Teller; Guggenheim-Anderson-De Boer(GAB); Peleg; and modified GAB. Isosteric heats of sorption were evaluated through the direct use of sorption isotherms by means of the Clausius-Clapeyron equation. Statistical Analysis Used: The sorption model parameters were determined from the experimental sorption data using nonlinear regression analysis, and mean relative percentage deviation(P), correlation(Correl), root mean square error, and model efficiency were considered as the criteria to select the best fit model. Results: The sorption–desorption isotherms have sigmoidal shape–confirming to TypeII isotherms. Based on the statistical data analysis, modified GAB model was found to be more adequate to explain sorption characteristics of CDP. It is noted that the rate of adsorption and desorption is specific to the temperature at which it was being studied. It is observed that isosteric heat of sorption decreased with increasing equilibrium moisture content. Conclusions: The calculation of the thermodynamic properties was further used to draw an understanding of the properties of water and energy requirements associated with the sorption behavior. The sorption–desorption data and the set of equations are useful in the simulation of processing, handling, and storage of CDP and further behavior during manufacture and storage of CDP formulations.

Keywords: Carvedilol, isotherm, model fitting, sorption, thermodynamic

How to cite this article:
Allada R, Maruthapillai A, Palanisamy K, Chappa P. Moisture sorption–desorption characteristics and the corresponding thermodynamic properties of carvedilol phosphate. J Pharm Bioall Sci 2017;9:16-21

How to cite this URL:
Allada R, Maruthapillai A, Palanisamy K, Chappa P. Moisture sorption–desorption characteristics and the corresponding thermodynamic properties of carvedilol phosphate. J Pharm Bioall Sci [serial online] 2017 [cited 2021 Jan 23];9:16-21. Available from:

   Introduction Top

Carvedilol phosphate(CDP), chemically (2RS)-1-(9H-Carbazol-4-yloxy)-3-[2-(2-methoxyphenoxy) ethyl] amino] propan-2-ol phosphate salt[Figure1], is indicated for the treatment of hypertension, mild to severe congestive heart failure, and left ventricular dysfunction, following heart attack. It is a nonselective beta/alpha-1 blocker and belongs to the third-generation beta-blockers.[1],[2] It is available with a brand name, Coreg CR ® for once-a-day administration as controlled release oral capsules containing 10, 20, 40, or 80mg CDP.
Figure 1: Molecular structure of carvedilol phosphate

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Physical characterization of pharmaceutical solids is gaining much importance in recent years due to the well-established understanding on impact of the variability in physical properties on formulation performance, process ability, product description, and stability.[3],[4],[5] A systematic and comprehensive physical characterization to obtain all the information is very much needed during the development of either a generic drug product or a new drug product. Temperature and humidity are known to be important factors that may affect product quality during the manufacturing process, packaging, and storage.[6],[7],[8],[9] The current study focuses on interaction with humidity/moisture. The interaction of moisture with pharmaceutical solids is greatly crucial to understand process hurdles, solid form transformations–especially hydration/dehydration, impact on glass transition in case of amorphous solids, mechanical properties, physical and chemical stability, dissolution rate, and finally the product performance(in vivo).[10],[11],[12] The moisture uptake studies are extremely important in design and optimizing manufacturing process parameters(suitable environmental and equipment settings), calculating water content specifications, and selecting appropriate packaging configuration.[13],[14]

In this research, the moisture sorption–desorption isotherms of CDP were determined using dynamic vapor sorption (DVS) technique. The isotherms explain the relationship between the equilibrium moisture content (EMC) and water activity at a constant temperature and pressure. Due to its shorter equilibration times and ability to obtain adsorption rate under constant or varying hydration conditions, DVS technique has been proven to be very advantageous over conventional static gravimetric technique.[15]

There are many theoretical models that have been proposed in the literature for the study of sorption–desorption isotherms.[16] They comprise models deduced theoretically and centered on thermodynamic considerations such as the Brunauer, Emmett, and Teller(BET)-a kinetic model based on monolayer,[17] the Guggenheim-Anderson-De Boer(GAB)-a kinetic model based on multilayer,[18] and some semiempirical and empirical models such as Peleg, Viollaz, and Rovedo.[19] Net isosteric sorption heat(qst) is a thermodynamic parameter, which is very useful for the process of moisture sorption and desorption that takes place in a material.[20] It can be calculated using the sorption data generated at different temperatures. Its value can be determined using Clausius-Clapeyron equation.

   Materials and Methods Top


CDP sample with initial water content of 1.78% was obtained from PharmaTrain(Hyderabad, India). The sample contained more than 99% purity. The sample was pretreated by drying at 40°C under nitrogen gas flow, before subjecting to different humidity and temperatures as per the study. Nitrogen gas used for all DVS experiments was of ultrapure grade(purity more than 99%).

Moisture sorption–desorption isotherms determination

The sorption–desorption isotherms of CDP were determined using DVS. The DVS experiments were conducted using Q5000 SA(TA Instruments, USA), consisting vertical nulling microbalance in which sample and reference crucibles are inserted in a chamber, where humidity and temperature can be controlled. The instrument can precisely control humidity(in the range 0%–98% relative humidity[RH]) and temperature(up to 85°C). Ultrapure nitrogen gas purging ensures stable microbalance. Separately, another steam of nitrogen is divided into two parts to attain desired humidity; this mixing is precisely controlled using high precise mass flow controllers. Desired humidity-temperature program can be executed using instrument software. The resulted data were exported into Microsoft Excel and processed further. Sorption isotherms were determined at ten RH values (0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% RH) and the isotherms were obtained at different temperatures(25°C, 30°C, and 40°C). The basis of selected temperatures is to be in-line with the general stability study conditions(long-term 25°C-60% RH; intermediate 30°C-65% RH; and accelerated 40°C-75% RH) as per the International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.

Moisture sorption–desorption data analysis: Model fitting

The sorption data obtained at three different temperatures(25°C, 30°C, and 40°C) were fitted tofour sorption models: BET, Peleg, and GAB and modified GAB [Table 1]. These models were chosen because these are most widely used to adjust experimental data to sorption isotherms. The sorption model parameters were determined from experimental sorption data using nonlinear regression analysis, and the mean relative percent deviation(P), correlation(Correl), root mean square error(RMSE), and model efficiency(ME) were considered as the criteria to select the best fit model. P value lower than 10% is considered as one of the criteria for model selection. The closeness between 'correlation value' and 'one' indicates the betterment of a model fitting.The RMSE indicates the deviation of experimental data from that of predicted and it is required to approach zero. The ME also provides the ability of a model and its highest value is 1. These statistical values were calculated using the following equations(Equations 1–5). The usefulness of the models may also be assessed by considering the number of parameters involved.
Table 1: Different models for fitting the experimental data of sorption isotherms and their range of applicability aw along with equation numbers

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Equation 1:

Equation 2:

Equation 3:

Equation 4:

Equation 5:

Where ME, MP, MEmean, and MPmean are the i th experimentally determined EMC, i th predicted EMC, mean value of experimentally determined EMC, and mean value of EMC predicted by the model, respectively.

Determination of isosteric heat of sorption

The Clausius-Clapeyron equation was used to determine net isosteric heat of sorption using the moisture sorption data. The equation is generally used to determine temperature effect on isotherms. The equation is simple, accurate, and applicable over a wide range of temperature. The equation is given below:

Equation 6:

Where qst is net isosteric heat of sorption(J/mol), aw is water activity, T is absolute temperature, and R is universal gas constant(8.314J/mol/K). The slope(−qst/R) of the above equation is obtained by plotting ln(aw) versus T −1 at a constant moisture; further, the qst can be calculated from the slope value.

In this study, the sorption data generated at three different temperatures 298, 303, and 313 K were used, with a water activity(aw) ranging from 0.04 to 0.89. The three values of aw corresponding to each of the temperatures 298, 303, and 313 K were obtained from sorption data for a particular value of EMC, and then, the slope values(using above Equation 6) are obtained to finally calculate net isosteric heat of sorption(qst). The approach was followed to calculate the qst values at seven different EMC: 0.6, 1.2, 1.8, 2.4, 3.0, 3.6, and 4.2%w/w. The qst values were plotted against EMC to see the relation between EMC and net isosteric heat of sorption(qst).

   Results and Discussion Top

Moisture sorption–desorption data analysis: Model fitting

Sorption and desorption isotherms of CDP, generated at different temperatures of 25, 30, and 40°C, are shown in [Figure2] and [Figure3], respectively. It is evident from the graphs that at a given value of aw, the corresponding EMC decreases with increase in temperature. All isotherms were of sigmoidal shape and correspond to TypeII as per the Brunauer's classification.[21] The figures indicate the effect of temperature on sorption–desorption rate. The thermodynamic properties calculated using mathematical modeling of experimental data at different temperatures using equations mentioned in [Table 1] are compiled in [Table2],[Table3],[Table4],[Table5] for BET, Peleg, GAB, and modified GAB, respectively. The maximum values of EMC(considered at about 90% RH) were found to be 5.43%, 4.57%, and 4.14%w/w at 25°C, 30°C, and 40°C, respectively. Such study, on raw materials of a drug product, gives crucial information about the total moisture contribution, which further can be used to fix specification for “water content” of the corresponding drug product. Statistical parameters(P, RMSE, modeling efficiency, Chi-square, and Correl) were evaluated for each of the model. The results indicate that modified GAB model appeared to be the best with a Correl value of 0.9982 and RMSE value of 0.0807, explains moisture sorption behavior of CDP. The next closely fitting model was found to be GAB with a Correl value of 0.9914 and RMSE value of 0.1726.
Figure 2: Sorption data of carvedilol phosphate, obtained at different temperatures 25°C (◊), 30°C (◻), and 40°C (Δ). The discrimination indicates temperature-dependent sorption behavior

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Figure 3: Desorption data of carvedilol phosphate, obtained at different temperatures 25°C (◊), 30°C (◻), and 40°C (Δ). The discrimination indicates temperature-dependent desorption behavior

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Table 2: Statistical parameters of Brunauer, Emmett, and Teller model when fitted to sorption data of carvedilol phosphate

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Table 3: Statistical parameters of Peleg model when fitted to sorption data of carvedilol phosphate

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Table 4: Statistical parameters of Guggenheim.Anderson.De Boer model when fitted to sorption data of carvedilol phosphate

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Table 5: Statistical parameters of modified Guggenheim-Anderson-De Boer model when fitted to sorption data of carvedilol phosphate

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Isosteric heat of sorption

The qst values, determined using Clausius-Clapeyron equation, were plotted against moisture content; the plot is represented in [Figure4]. It is seen in [Figure4] that the net isosteric heat of sorption has strong dependence on moisture content; the value of qst decreases with increasing moisture content. This infers initial filling of highly active polar portions on the surface(with the high interaction energy), followed by the subsequent filling of the less active available portions with lesser bonding activation energies. It can be deduced from [Figure 4] that the values of heat of sorption approached to heat of vaporisation of pure water, indicating that the moisture is existing in the free form. The value of qst indicates the heat supply for drying of a material. As it varies with moisture content, the property determines the temperature dependence of water activity of a material. The extent of moisture content, at which the value of qst exceeds heat of vaporization of pure water, is commonly considered as an indication of the amount of bound water.[22] Thermodynamically, it is a positive quantity when heat is evolved during adsorption, and negative when heat is absorbed during desorption. In other words, the heat of adsorption can be described as a measure of the energy released on sorption, and the heat of desorption as the energy required for breaking the forces between the molecules of water vapor and the surface of adsorbent material. Therefore, the qst is also considered as indicative of the intermolecular attractive forces.[23] The value of qst is used as a thermodynamic function for analysis of moisture sorption isotherms. The application of thermodynamic principles to moisture sorption isotherms has been utilized to obtain more information of water and surface interactions and kinetics. The values are also useful to optimize drying conditions of a material when handled at different RH values.
Figure 4: Isosteric heat of sorption of carvedilol phosphate as a function of equilibrium moisture content

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   Conclusions Top

The sorption–desorption data of CDP were obtained at three different temperatures of 25°C, 30°C, and 40°C using DVS; the results indicated that the EMC increased as the temperature decreased, at constant RH. In addition, at constant temperature, EMC is increased as the RH increased. This information can readily be used to understand hygroscopicity of CDP, thereby to optimize drug handling conditions. The isotherms of CDP were found to correspond to typical TypeII as per the Brunauer's classification. Based on statistical parameters(calculated for each model at the three temperatures of 5°C, 20°C, and 45°C studied for adsorption), modified GAB model was the one that best explained when compared with the other models studied. It is, thus, concluded that the modified GAB model is most suitable for describing the sorption isotherms of CDP in the temperature range of 25–40°C and RH range of 5%–90%. The isosteric heat of sorption values of CDP was determined using Clausius-Clapeyron equation, and the observed values were found to be decreasing with increase in moisture content; this phenomenon showed power relationship with moisture content. The sorption–desorption data and the set of equations will be useful in the simulation of processing, handling, and storage of CDP and further behavior during manufacture and storage of CDP formulations.


We wish to thank PharmaTrain(Hyderabad, India) for the gift sample of CDP(the main material) and all necessary instrumentation for supporting this work.

Financial support and sponsorship

Instrumentation and analytical support was obtained from PharmaTrain, Hyderabad.

Conflicts of interest

There are no conflicts of interest.

   References Top

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  [Figure1], [Figure2], [Figure3], [Figure4]

  [Table 1], [Table2], [Table3], [Table4], [Table5]


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